A variety of approaches have been developed for administering a biologically active agent to a patient in a continuous or sustained manner. However, currently available approaches suffer from one or more disadvantages or limitations.
In many conventional controlled release systems, the active agents are incorporated into solid, monolithic polymeric matrices. The matrices are surgically implanted into patients' bodies and control the release of active agents into the patients' systems. Often, however, the sizes and shapes of the matrices and the surgical implantation lead to patient discomfort and complications. In recent years, microstructures, such as lipospheres, liposomes, microcapsules, microparticles, and nanoparticles have been developed to overcome these problems. The microstructures contain the active agents and are introduced into a patients' bodies as dispersions. However, when inserted into a body cavity where there is considerable fluid flow, such as the mouth or eye, microstructures may be poorly retained due to their small size and discontinuous nature. Microstructure systems also lack reversibility. If complications arise after introduction, it is difficult to remove the microstructures without extensive and complex surgical intervention.
Other controlled release delivery systems are flowable composition that can be administered using a syringe. Upon contact with body fluids, the delivery system is transformed in situ to form a solid implant. Exemplary flowable polymeric compositions are described in U.S. Pat. Nos. 4,938,763; 5,278,201; and 5,278,202. As the delivery system forms a solid matrix, the active agent is trapped or encapsulated within the matrix. The release of the active agent then follows the general rules for the dissolution or diffusion of a drug from within a polymeric matrix.
Irrespective of their physical character as monolithic matrices, microstructures or flowable compositions, these delivery systems can not be effectively used with all biologically active agents. Some biologically active agents may be destroyed or dissolved by the polymeric formulations and carriers used in these systems. For example, peptides or proteins may be denatured by the solvents used to dissolve the polymers. RNA or DNA compounds and antigens may be affected. Cellular treatments are also difficult to administer using known sustained release systems. The sustained release formulations often provide an environment that is too harsh for cellular survival and therefore causes destruction or death of the cells. Therefore, an improved method for sustained release of a biologically active agent in which the active agent is protected from the sustained release formulation would be desirable.